Albert J. Bredenoord

Chicago classification criteria of esophageal motility disorders defined in high resolution esophageal pressure topography.

Background  The Chicago Classification of esophageal motility was developed to facilitate the interpretation of clinical high resolution esophageal pressure topography (EPT) studies, concurrent with the widespread adoption of this technology into clinical practice. The Chicago Classification has been an evolutionary process, molded first by published evidence pertinent to the clinical interpretation of high resolution manometry (HRM) studies and secondarily by group experience when suitable evidence is lacking.

Determinants of perception of heartburn and regurgitation

Background and aim: It is not known why some reflux episodes evoke symptoms and others do not. We investigated the determinants of perception of gastro-oesophageal reflux. Methods: In 32 patients with symptoms suggestive of gastro-oesophageal reflux, 24 hour ambulatory pH and impedance monitoring was performed after cessation of acid suppressive therapy. In the 20 patients who had at least one symptomatic reflux episode, characteristics of symptomatic and asymptomatic reflux episodes were compared. Results: A total of 1807 reflux episodes were detected, 203 of which were symptomatic. Compared with asymptomatic episodes, symptomatic episodes were associated with a larger pH drop (p<0.001), lower nadir pH (p<0.05), and higher proximal extent (p<0.005). Symptomatic reflux episodes had a longer volume and acid clearance time (p<0.05 and p<0.002). Symptomatic episodes were preceded by a higher oesophageal cumulative acid exposure time (p<0.05). The proximal extent of episodes preceding regurgitation was larger than those preceding heartburn; 14.8% of the symptomatic reflux episodes were weakly acidic. In total, 426 pure gas reflux episodes occurred, of which 12 were symptomatic. Symptomatic pure gas reflux was more frequently accompanied by a pH drop than asymptomatic gas reflux (p<0.05). Conclusions: Heartburn and regurgitation are more likely to be evoked when the pH drop is large, proximal extent of the refluxate is high, and volume and acid clearance is delayed. Sensitisation of the oesophagus occurs by preceding acid exposure. Weakly acidic reflux is responsible for only a minority of symptoms in patients off therapy. Pure gas reflux associated with a pH drop (“acid vapour”) can be perceived as heartburn and regurgitation.

Oesophageal high-resolution manometry: moving from research into clinical practice

Manometry measures pressure within the oesophageal lumen and sphincters, and provides an assessment of the neuromuscular activity that dictates function in health and disease. It is performed to investigate the cause of functional dysphagia, unexplained “non-cardiac” chest pain, and in the pre-operative work-up of patients referred for anti-reflux surgery. Manometric techniques have improved in a step-wise fashion from a single pressure channel to the development of high-resolution manometry (HRM) with up to 36 pressure sensors. At the same time, advances in computer processing allow pressure data to be presented in real time as a compact, visually intuitive “spatiotemporal plot” of oesophageal pressure activity. HRM recordings reveal the complex functional anatomy of the oesophagus and its sphincters. Spatiotemporal plots provide objective measurements of the forces that move food and fluid from the pharynx to the stomach and determine the risk of reflux events. The introduction of commercially available HRM has been followed by rapid uptake of the technique. This review examines the current evidence that supports the move of HRM from the research setting into clinical practice. It is assessed whether a detailed description of pressure activity identifies clinically relevant oesophageal dysfunction that is missed by conventional investigation, increasing diagnostic yield and accuracy. The need for a new classification system for oesophageal motor activity based on HRM recordings is discussed. Looking ahead the potential of this technology to guide more effective medical and surgical treatment of oesophageal disease is considered because, ultimately, it is this that will define the success of HRM in clinical practice.

Peroral Endoscopic Myotomy for the Treatment of Achalasia: An International Prospective Multicenter Study

Pilot studies have indicated that peroral endoscopic myotomy (POEM) might be a safe and effective treatment for achalasia. We performed a prospective, international, multicenter study to determine the outcomes of 70 patients who underwent POEM at 5 centers in Europe and North America. Three months after POEM, 97% of patients were in symptom remission (95% confidence interval, 89%-99%); symptom scores were reduced from 7 to 1 (P < .001) and lower esophageal sphincter pressures were reduced from 28 to 9 mm Hg (P < .001). The percentage of patients in symptom remission at 6 and 12 months was 89% and 82%, respectively. POEM was found to be an effective treatment for achalasia after a mean follow-up period of 10 months.

Esophageal pH-Impedance Monitoring in Patients With Therapy-Resistant Reflux Symptoms: 'On' or 'Off' Proton Pump Inhibitor?

BACKGROUND:In patients with proton pump inhibitor (PPI)-resistant symptoms, ambulatory 24-h pH-impedance monitoring can be used to assess whether a relationship exists between symptoms and reflux episodes. Until now, it is unclear whether combined pH-impedance monitoring in these patients should be performed on or off PPI.METHODS:Thirty patients with symptoms of heartburn, chest pain, and/or regurgitation despite PPI twice daily underwent ambulatory 24-h pH-impedance monitoring twice, once on PPI and once after cessation of the PPI for 7 days. The order of the measurements was randomized. Reflux episodes were identified and classified as acid, weakly acidic, or weakly alkaline reflux. In addition, the symptom association probability (SAP) was calculated for each measurement.RESULTS:The total number of reflux episodes and proximal extent were not affected by PPI therapy. On PPI, there were fewer acid reflux episodes (49 ± 34 off PPI vs 20 ± 25 on PPI) while more weakly acidic reflux episodes were identified (24 ± 17 off PPI vs 48 ± 31 on PPI). Symptom association analysis identified 15 and 11 patients with a positive SAP in the measurement off and on PPI, respectively, the difference in yield of the SAP not being statistically significant. Eight of the 19 patients who had no symptoms or a negative SAP during measurement on PPI had a positive SAP off PPI therapy. In contrast, only 4 patients with a positive SAP on PPI were missed in the measurement off PPI therapy.CONCLUSIONS:In order to demonstrate or exclude GERD in patients with PPI-resistant symptoms, ambulatory 24-h pH-impedance monitoring should preferably be performed after cessation of PPI therapy because this approach seems to offer the best chance to assess a relationship between symptoms and reflux episodes.

Addition of esophageal impedance monitoring to pH monitoring increases the yield of symptom association analysis in patients off PPI therapy

BACKGROUND:The additional yield of esophageal impedance monitoring in identification of reflux as the cause of reflux symptoms is unknown.OBJECTIVES:To compare the yield of symptom–reflux association analysis of combined esophageal pH-impedance data with the yield of analysis of pH data alone.METHODS:In 60 patients with symptoms of heartburn and regurgitation combined, 24-h pH-impedance monitoring was performed. Acid-suppressive medication was stopped 1 wk in advance. Patients (48) with at least one symptom during the measurement period were selected for further analysis. Patients were instructed to note the time and nature of their symptoms. Eleven types of reflux episodes were defined, based on combinations of magnitude of the pH drop, nadir pH, and nature of the refluxate (gas and liquid) on impedance tracings. Symptom association analysis—symptom index, the symptom sensitivity index, and the symptom association probability (SAP)—was performed for each definition of reflux.RESULTS:The proportion of patients with a positive SAP (≥95.0%) varied between 62.5% and 77.1%, depending on the definition of reflux episodes. When both pH and impedance parameters were used to identify reflux, a higher proportion of patients had a positive SAP than with pH alone (77.1%vs 66.7%, p < 0.05). Symptom association analysis for acidic and weakly acidic reflux separately did not result in a higher yield than analysis with all reflux episodes pooled, regardless of pH.CONCLUSION:In patients off proton pump inhibitor, the addition of impedance monitoring to esophageal pH monitoring leads to an increase in the proportion of patients in whom an association between reflux episodes and symptoms can be identified.

Esophageal acid exposure decreases intraluminal baseline impedance levels.

OBJECTIVES:Intraluminal baseline impedance levels are determined by the conductivity of the esophageal wall and can be decreased in gastroesophageal reflux disease (GERD) patients. The aim of this study was to investigate the baseline impedance in GERD patients, on and off proton pump inhibitor (PPI), and in healthy controls.METHODS:Ambulatory 24-h pH–impedance monitoring was performed in (i) 24 GERD patients with and 24 without pathological esophageal acid exposure as well as in 10 healthy controls and in (ii) 20 patients with refractory GERD symptoms despite PPI, once on PPI and once off PPI. Baseline impedance levels in the most distal and the most proximal impedance channels were assessed.RESULTS:Median (interquartile range) distal baseline impedance in patients with physiological (2,090 (1,537–2,547) Ω) and pathological (781 (612–1,137) Ω) acid exposure was lower than in controls (2,827 (2,127–3,270) Ω, P<0.05 and P<0.001). A negative correlation between 24-h acid exposure time and baseline impedance was observed (r=−0.7, P<0.001). In patients measured off and on PPI, median distal baseline impedance off PPI was significantly lower than on PPI (886 (716–1,354) vs. 1,372 (961–1,955) Ω, P<0.05) and distal baseline impedance in these groups was significantly lower than in healthy controls (P<0.05 and P<0.001). Proximal baseline impedance did not differ significantly between the patients off PPI and on PPI (1,793 (1,384–2,489) vs. 1,893 (1,610–2,561) Ω); however, baseline impedance values in both measurements were significantly lower than in healthy controls (3,648 (2,815–3,932) Ω, both P<0.001).CONCLUSIONS:These findings suggest that baseline impedance is related to esophageal acid exposure and could be a marker of reflux-induced changes to the esophageal mucosa.

Proton pump inhibitor-responsive oesophageal eosinophilia: an entity challenging current diagnostic criteria for eosinophilic oesophagitis

Consensus diagnostic recommendations to distinguish GORD from eosinophilic oesophagitis (EoE) by response to a trial of proton pump inhibitors (PPIs) unexpectedly uncovered an entity called ‘PPI-responsive oesophageal eosinophilia’ (PPI-REE). PPI-REE refers to patients with clinical and histological features of EoE that remit with PPI treatment. Recent and evolving evidence, mostly from adults, shows that patients with PPI-REE and patients with EoE at baseline are clinically, endoscopically and histologically indistinguishable and have a significant overlap in terms of features of Th2 immune-mediated inflammation and gene expression. Furthermore, PPI therapy restores oesophageal mucosal integrity, reduces Th2 inflammation and reverses the abnormal gene expression signature in patients with PPI-REE, similar to the effects of topical steroids in patients with EoE. Additionally, recent series have reported that patients with EoE responsive to diet/topical steroids may also achieve remission on PPI therapy. This mounting evidence supports the concept that PPI-REE represents a continuum of the same immunological mechanisms that underlie EoE. Accordingly, it seems counterintuitive to differentiate PPI-REE from EoE based on a differential response to PPI therapy when their phenotypic, molecular, mechanistic and therapeutic features cannot be reliably distinguished. For patients with symptoms and histological features of EoE, it is reasonable to consider PPI therapy not as a diagnostic test, but as a therapeutic agent. Due to its safety profile, ease of administration and high response rates (up to 50%), PPI can be considered a first-line treatment before diet and topical steroids. The reasons why some patients with EoE respond to PPI, while others do not, remain to be elucidated.

Ten-year outcome of laparoscopic and conventional nissen fundoplication: randomized clinical trial.

Objective:To compare 10 years outcome of a multicenter randomized controlled trial on laparoscopic (LNF) and conventional Nissen fundoplication (CNF), with focus on effectiveness and reoperation rate. Summary of Background Data:LNF has replaced CNF as surgical treatment for gastroesophageal reflux disease (GERD). Decisions are based on equal short-term effectiveness and reduced morbidity, but confirmation by long-term level 1 evidence is lacking. Methods:From 1997 to 1999, 177 proton pump inhibitor (PPI)-refractory GERD patients were randomized to undergo LNF or CNF. The 10 years results of surgery on reflux symptoms, general health, PPI use, and reoperation rates, are described. High-resolution manometry, 24-hour pH-impedance monitoring and barium swallow were performed in symptomatic patients only. Results:A total of 148 patients (79 LNF, 69 CNF) participated in this 10-year follow-up study. GERD symptoms were relieved in 92.4% and 90.7% (NS) after LNF and CNF, respectively. Severity of heartburn and dysphagia were similar, but slightly more patients had relief of regurgitation after LNF (98.7% vs. 91.0%; P = 0.030). The percentage of patients using PPIs slowly increased with time in both groups to 26.6% for LNF and 22.4% for CNF (NS). General health (74.7% vs. 72.7%; NS) and quality of life (visual analogue scale score: 65.3 vs. 61.4; NS) improved similarly in both groups. The percentage of patients who would have opted for surgery again was similar as well (78.5% vs. 72.7%; NS). Twice as many patients underwent reoperation after CNF compared with LNF (12 [15.2%] vs. 24 [34.8%]; P = 0.006), including a higher number of incisional hernia corrections (2 vs. 9; P = 0.015). Mean interval between operation and reintervention was longer after CNF (22.9 vs. 50.6 months; P = 0.047). Of the patients who were dependent on daily PPI therapy at 10 years (LNF 10, CNF 10), 7 patients (LNF 3, CNF 4) had recurrent GERD on pH-impedance monitoring, 5 of them with some form of anatomic recurrence. A total of 13 of 20 (65.0%) patients did not have recurrent GERD. Fourteen patients had an abnormal high-resolution manometry. Conclusions:CNF carries a higher risk for surgical reintervention compared with LNF, mainly due to incisional hernia corrections. The 10-year effectiveness of LNF and CNF is comparable in terms of improvement of GERD symptoms, PPI use, quality of life, and objective reflux control. Consequently, the long-term results from this trial lend level 1 support to the use of LNF as the surgical procedure of choice for GERD.

Rapidly increasing incidence of eosinophilic esophagitis in a large cohort

Background  Recent literature has shown increasing incidence and prevalence rates of eosinophilic esophagitis (EoE). However, data are mainly based on small studies and come from centers dedicated to EoE. Aim of this study was to estimate the incidence rates of EoE by using a large database.